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Biomedical subjects

K O'Malley

Publications and source records attributed to K O'Malley.

At least 73 records · Page 4Linked to original sources
PubMed1991

Hepatic beta-adrenoceptor adaptation during propranolol administration is impaired in aging rats.

Aging has been associated with changes in beta-adrenoceptor responses and adaptation to prolonged removal of catecholamine stimulation. We have examined the effect of chronic propranolol administration on rat hepatic membrane beta-adrenoceptor density, agonist affinity and response in young (6-7 months) and old (26-7 months) male Wistar rats. Propranolol administration via miniosmotic pumps for 7 days resulted in similar and sustained plasma propranolol levels (approximately 100 ng/ml) in old and young rats. Pretreatment beta-adrenoceptor responses to isoprenaline were significantly higher in old rats. Propranolol administration was associated with significant increases in beta-adrenoceptor response and density (Bmax) in young rats only. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) responses to prostaglandin E1 (PGE1), guanosine triphosphate (GTP), 5'-guanyl-imidodiphosphate (Gpp(NH)p), forskolin and Mn2+ were not significantly different between young and old rats and were not affected by propranolol administration. Neither aging or propranolol administration was associated with a change in beta-adrenoceptor agonist affinity. These findings demonstrate elevated hepatic beta-adrenoceptor response and impaired hepatic beta-adrenoceptor adaptation to beta-adrenoceptor blockade in aging rats.

Adaptation, Physiological↗
PubMed1991

Further learnings from the European Working Party on High Blood Pressure in the Elderly (EWPHE) study: focus on systolic hypertension.

Event rates in relation to the number of elderly hypertensives treated were calculated from randomized analysis data from the 840 patients who completed the European Working Party on High Blood Pressure in the Elderly (EWPHE) trial. In all, the actively treated group had 29 fewer cardiovascular events per 1000 patient years. Putting this another way, treating 34 patients for 1 year would prevent one cardiovascular event. Moreover, as there were 14 fewer cardiovascular deaths and 11 fewer nonfatal strokes per 1000 patient years in the actively treated groups, we calculated that treating 71 or 91 elderly patients for 1 year would prevent one cardiovascular death or nonfatal stroke, respectively. Because of the higher baseline incidence of cardiovascular events in this study, there were greater gains in terms of absolute reductions in mortality and morbidity in treated elderly hypertensive patients than in younger patients in similar studies. Of the 840 patients who participated in the trial, 247 had systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure less than or equal to 95 mmHg. In this group, blood pressure was reduced by 13/8 mmHg after 3 years in those randomized to active treatment compared to placebo. While patient numbers were insufficient to draw firm conclusions, their outcome on treatment was similar to that for patients on active treatment in the overall study. These results high-light the need for a rigorous assessment of the value of treating isolated systolic hypertension in the elderly.

Aged↗
PubMed1991

Upper limb embolus: a timely diagnosis.

In a ten year period, 36 patients were treated surgically for embolic occlusion of upper limb vessels. The sources of embolus were cardiac (58%), peripheral aneurysm (22%) and unknown (20%). Brachial embolectomy was performed in all cases. Six out of eight peripheral aneurysms were resected. A patency rate of 94% was achieved at five years. Hospital mortality and morbidity rates were 3% and 10%, respectively. One patient died of a myocardial infarct one week postoperatively. Three patients suffered ischemic contracture or amputation; all three presented after 36 hours. We conclude that upper limb emboli are usually easy to recognize and treat. Prompt surgery (less than 24 hours) produces the most satisfactory results. Late presentation or delay in treatment can result in limb loss.

Acute Disease↗
PubMed1991

Ambulatory blood pressure monitoring in the evaluation of drug efficacy.

Conventional clinic measurement of blood pressure is influenced by many factors that make the technique unsuitable for the assessment of antihypertensive drug efficacy. The major drawback of conventional measurement is that it cannot indicate the duration of drug effect or the influence of antihypertensive drugs on nocturnal blood pressure. Noninvasive 24-hour ambulatory blood pressure measurement has a number of advantages over conventional measurement: it provides a profile of blood pressure over the 24-hour period; it detects white coat responders; it is free of regression to the mean and the placebo response, thereby making it possible to consider efficacy studies which need not have a placebo phase; it enables considerably more observations than is possible with clinic measurement by increasing the power of studies, which may reduce significantly the numbers of patients needed for antihypertensive drug studies. Twenty-four-hour ambulatory blood pressure measurement offers the opportunity to study antihypertensive drugs in fewer patients with greater accuracy than is possible with conventional clinic measurement and should be a mandatory requirement for such studies.

Ambulatory Care↗
PubMed1991

Clinical benefits of structural and functional changes with calcium antagonists.

Calcium antagonists have a large variety of pharmacologic effects in addition to those exploited clinically. All drugs used in the management of hypertension, including calcium antagonists, are coming under increasing scrutiny for the possible beneficial and adverse effects they may have on the circulation and risk factor profile. This is particularly because of concern about the relative resistance of coronary heart disease to antihypertensive drug treatment and the increasing interest in evaluating the impact of blood pressure-lowering drugs on surrogate endpoints such as left ventricular hypertrophy. Given the pharmacokinetic and pharmacodynamic heterogeneity of calcium antagonists, it may be wise to keep in mind the subtypes as exemplified by the prototypes nifedipine, diltiazem, and verapamil and to extrapolate from one type to another with great caution. The increased understanding of the diversity among calcium antagonists as well as the pathophysiology of hypertension and other vascular diseases promises an exciting future for calcium antagonists in cardiovascular therapeutics.

Calcium Channel Blockers↗
PubMed1991

Choice of drug treatment for elderly hypertensive patients.

It is generally agreed that moderate and severe hypertension in the elderly should be treated, but it is not clear which drug or drugs are most appropriate. Thiazide diuretics are inexpensive and effective, but they are associated with metabolic side effects that are becoming less acceptable as newer agents become available. Beta blockers are effective, but can be associated with central nervous system side effects and are often contraindicated by coexisting disease. Recently, attention has been focused on the newer agents, including calcium antagonists and angiotensin-converting enzyme inhibitors. The advantage of calcium antagonists is that they do not produce metabolic side effects. However, they are expensive and may cause vasodilatory side effects. The angiotensin-converting enzyme inhibitors are effective and relatively free of side effects and may be particularly useful for elderly hypertensive patients with congestive heart failure.

Aged↗
PubMed1991

Neutrophil beta-adrenergic receptor responses are potentiated by acute exposure to phorbol ester without changes in receptor distribution or coupling.

Exposure to the phorbol ester, phorbol 12-myristate, 13-acetate (PMA, 100nM) for 10 minutes enhanced cyclic AMP accumulation in human neutrophils under basal conditions and in response to the beta-adrenergic receptor agonist isoproterenol (ISO), 1 microM) and the adenylate cyclase activator forskolin (FSK, 10mM). Potentiation of responses to ISO by PMA was dose-dependent between 0.1 and 100nM PMA. The diacylglycerol analogue, 1-oleoyl-2-acetylglycerol (OAG) (50 microM) also elevated beta-receptor responses, but 4 beta-phorbol (100nM), lacking the capacity to activate PMA, was ineffective. Short-term exposure (12 seconds) to the peptide n-formylmethionine leucyl-phenylalanine (FMLP, 1 microM) also elevated neutrophil cyclic AMP accumulation. All potentiating effects of PMA on cyclic AMP production were inhibited by the protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7). Elevation of cyclic AMP by FMLP was insensitive to H7. PMA had no apparent effect on beta-receptor agonist-affinity, distribution between cell-surface and internalised compartments, or the capacity of ISO to induce beta-receptor internalisation. Responses to FSK or ISO in terms of fold-stimulation of basal cyclic AMP accumulation in the presence of PMA were not elevated by PMA. These findings indicate that PMA exerts a potentiating effect on neutrophil adenylate cyclase responses through protein kinase C activation. FMLP elevation of neutrophil cyclic AMP in the absence of other stimuli, appears however, to be insensitive to protein kinase inhibition.

Cells, Cultured↗
PubMed1991

Assessing the quality of life of the individual: the SEIQoL with a healthy and a gastroenterology unit population.

Current methods of measuring quality of life (QoL) impose an external value system on individuals, rather than allowing them to describe their lives in terms of those factors which they consider important. The Schedule for the Evaluation of Individual Quality of Life (SEIQoL) was developed to overcome such limitations. The QoL of 42 healthy attenders at an international immunization clinic was assessed using SEIQoL. Judgement reliability was high (r = 0.74) and individuals' judgement policies accounted for a large percentage of the variance in overall QoL (R2 = 0.75) demonstrating the construct validity of judgement analysis in this context. In a second study of QoL of out-patient suffering from irritable bowel syndrome (IBS) (N = 20) or peptic ulcer disease (PUD) (N = 20) was assessed using SEIQoL. Judgement reliability was lower (r = 0.54) although statistically highly significant (P less than 0.01), and the variance in overall QoL judgements explained was high (R2 = 0.74). SEIQoL is an acceptable, reliable and valid technique for measuring individual QoL that takes greater account of individual perspectives than traditional measurement approaches.

Activities of Daily Living↗
PubMed1991

Plasma atrial natriuretic peptide concentration and platelet atrial natriuretic peptide binding site density in ageing and hypertension.

1. Ageing and hypertension are associated with changes in the way in which the body handles sodium. This may involve changes in plasma atrial natriuretic peptide concentration, since atrial natriuretic peptide is a regulator of sodium handling by the kidney and the plasma atrial natriuretic peptide concentration is increased in both ageing and hypertension. An increase in the plasma atrial natriuretic peptide concentration could also be associated with a change in atrial natriuretic peptide receptor density, possibly involving down-regulation. 2. To investigate these possibilities plasma atrial natriuretic peptide concentration and platelet atrial natriuretic peptide binding site density were measured in 18 young, 11 middle-aged and 12 elderly healthy subjects and in 23 patients with mild to moderate essential hypertension. 3. In normotensive subjects, the plasma atrial natriuretic peptide concentration increased with age (r = 0.49, P less than 0.01) and was significantly higher in elderly than young subjects (mean +/- SEM, 31.9 +/- 4.5 versus 18.3 +/- 2.0 pmol/l, P less than 0.05). The plasma atrial natriuretic peptide concentration increased with the mean arterial pressure in normotensive subjects (r = 0.47, P less than 0.01). Multiple regression analysis did not show independent relationships between the plasma atrial natriuretic peptide concentration and either age or mean arterial pressure in normotensive subjects alone. However, when normotensive subjects and hypertensive patients were considered together, multiple regression revealed both age and mean arterial pressure as independent predictors of the plasma atrial natriuretic peptide concentration (P less than 0.05, P less than 0.01, respectively). In normotensive subjects, the platelet atrial natriuretic peptide binding site density did not change with age (r = 0.19, P = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study.

In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).

Adult↗
PubMed1991

The effects of age on platelet intracellular free calcium concentrations in normotensives and hypertensives.

We have investigated relationships between age, blood pressure and intracellular calcium concentration in platelets from normotensives and hypertensives. In normotensives, there were positive correlations between age and platelet intracellular calcium concentration (r = 0.76, P less than 0.001), age and mean arterial pressure (MAP; r = 0.55, P less than 0.01) and MAP and platelet intracellular calcium concentration (r = 0.45, P less than 0.01). Multiple regression analysis revealed that age was the primary determinant of platelet intracellular calcium concentration in normotensives. The effect of MAP on platelet intracellular calcium concentration when adjusted for age was not significant (P = 0.73). In hypertensives, there was no significant relationship between age and platelet intracellular calcium concentration (r = 0.15, P = 0.43), age and MAP (r = 0.17, P = 0.37) or MAP and platelet intracellular calcium concentration (r = -0.27, P = 0.15). Overall, platelet intracellular calcium concentration was significantly higher in hypertensives than in age-matched normotensives (P less than 0.05). Within the age groups examined, platelet intracellular calcium concentration was significantly higher only in younger hypertensives when compared with controls of a similar mean age (P less than 0.001). Thus, age, in addition to hypertension, is an important determinant of platelet intracellular calcium concentration.

Adult↗
PubMed1991

Ambulatory blood pressure measurement in the diagnosis and management of hypertension.

Before the diagnostic potential of 24-hour non-invasive BP measurement can be assessed, the accuracy of ambulatory recorders must be established, and normal reference values determined. The accuracy criteria of four ambulatory BP measuring systems (the SpaceLabs 90207, the Novecor DIASYS 200, the Takeda TM-2420 and the Del Mar Avionics Pressurometer IV) have been assessed according to the British Hypertension Society (BHS) protocol, and the Medilog, Suntech Accutracker II and the SpaceLabs 90202 according to the standard of the Association for the Advancement of Medical Instrumentation (AAMI). The SpaceLabs 90202 and 90207, the DIASYS 200 and the Medilog fulfilled the AAMI criteria. The best devices with the BHS grading system are the SpaceLabs 90207 and the DIASYS 200. Normal reference values for daytime, night-time and 24-hour ambulatory BP have been provided by the Allied Irish Bank study of 815 healthy individuals, which showed clear age and sex differences. The mean 24-hour ambulatory pressure for the entire group was 118/72 mm Hg. 24-hour ambulatory BP measurement possesses clear advantages over conventional clinic measurement in evaluating drug efficacy, as it provides many more readings, allowing for the possibility of reducing the number of patients in antihypertensive drug studies and eliminating the need for a placebo-controlled crossover design. It allows assessment of night-time BP, which is important in view of the fact that excessive BP reduction may put patients at risk of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Validation requirements for ambulatory blood pressure measuring systems.

The increasing application of ambulatory blood pressure measurement in clinical practice has stimulated the manufacture of a large number of ambulatory systems which must be independently validated. The British Hypertension Society protocol for the evaluation of blood pressure measuring devices has now been used to evaluate eight ambulatory systems. Based on this experience recommendations are made for improving validation techniques for the evaluation of ambulatory devices.

Blood Pressure Monitors↗
PubMed1991

The role of twenty-four-hour ambulatory blood pressure measurement in clinical practice.

Twenty-four-hour ambulatory blood pressure monitoring is passing from research into clinical practice and it is necessary to clarify circumstances for which 24-h ambulatory measurement will be most beneficial. Devices should be accurate and reasonably priced. The operator should be able to interpret 24-h recordings and be familiar with the operation of the equipment. The subject must be capable of complying with the instructions necessary for successful use of the device. In diagnosis, 24-h ambulatory blood pressure measurement is particularly useful in deciding whether subjects with borderline hypertension have a genuinely elevated blood pressure, in identifying white-coat hypertension, in determining dipper status and in diagnosing symptomatic hypotension. In the management of antihypertensive drug treatment, the technique helps the clinician to select the drug best suited to the individual patient in terms of duration of action and suitability for the individual 24-h profile; the technique also identifies any excessive reduction in blood pressure and provides a means of assessing resistant cases of hypertension.

Antihypertensive Agents↗